The overall goal of this project is to test the hypothesis that the hypothalamic-pituitary-ovarian axis plays a permissive but necessary role in the etiology of psychoemotional and physical symptoms trained to the menstrual cycle. We have shown that healthy women who experience significant cycle-related symptoms exhibit normal neuroendocrine activity rather than a defect in either the central or ovarian regulators of the reproductive cycle. We propose that significant menstrual symptomatology requires a "backdrop" of normal ovulatory events but coupled with an exposure to novel or altered ranges of sex hormone secretion. Biologic processes known to influence sex steroid production such as weight change and aging, may precipitate an altered responsiveness to ovulation. These factors have been implicated as biologic triggers for premenstrual syndrome (PMS) but seldom controlled for or adequately studied in previous menstrual cycle research. Psychosocial factors (eg. feminine socialization) may influence the degree of susceptibility to symptoms associated with this new ovarian hormone milieu. To test this hypothesis, we plan to 1) continue the detailed assessment neuroendocrine regulation of ovulation in overweight women and women ages 40 to 45 with and without PMS and 2) examine neuroendocrine features and psychobiologic responses to sex steroid placement therapy in perimenopausal patients who differ in age, ovulatory function and psychosocial salience of menstruation. Women will be studied prior to and following the initiation cyclic ovarian hormone therapy. Well-established clinical protocols will be performed in the clinical Research Center of University Hospital to determine changes in pulsatile secretion of proteinizing hormone (LH) and progesterone (P), as well as basal production of follicle stimulating hormone (FSH) and estradiol (E2): hormones which have been proposed as the biologic determinants menstrual cycle symptoms. At each outpatient visit, LH pulsatility will be assessed from I ml blood samples collected from an IV line taken at 10 min intervals for 8 hrs (n=49). In ovulatory women, P pulsatility will be assessed q 30 min. Well-established radioimmunoassays will bc used for serial hormone determinations. We will continue to use the Woods Daily Health Diary to monitor menstrual symptoms and the Woods Women's Health Survey to assess psychosocial stressors, feminine socialization and health practices. These studies should extend our findings of the detailed nature the psychobiology of PMS and lead to a better understanding of the adaptational responses to menstruation in a variety of understudied women's health clients.